| 000 | 02882cam a2200205 4500500 | ||
|---|---|---|---|
| 005 | 20250112044755.0 | ||
| 041 | _afre | ||
| 042 | _adc | ||
| 100 | 1 | 0 |
_aWeinhard, Jules _eauthor |
| 700 | 1 | 0 |
_a Noble, Johan _eauthor |
| 700 | 1 | 0 |
_a Jouve, Thomas _eauthor |
| 700 | 1 | 0 |
_a Malvezzi, Paolo _eauthor |
| 700 | 1 | 0 |
_a Rostaing, Lionel _eauthor |
| 245 | 0 | 0 | _aImproving access to kidney transplantation for highly sensitized patients: What is the role of IL-6 pathway blockade in desensitization protocols? |
| 260 | _c2022. | ||
| 500 | _a75 | ||
| 520 | _aBackgroundDesensitization allows kidney transplantation for highly sensitized subjects. Due to the central role of IL-6 in immunological response, tocilizumab (a monoclonal antibody directed against the IL-6 receptor) could potentially improve the efficacy of desensitization.MethodsWe conducted a systematic review using the following MeSH terms in PubMed: tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft, and desensitization.StudiesIL-6 plays a role in humoral response (plasma cell differentiation induced by T cells, IL-21 secretion) as well as in cellular response (differentiation of T cells to Th17 rather than Treg). In desensitization, tocilizumab was first studied as a second-line treatment after failure of standard-of-care (apheresis and rituximab ± IgIV). A recent study showed that tocilizumab monotherapy attenuated anti-HLA antibody levels, but not enough to allow transplantation. However, lymphocyte immunophenotyping showed that tocilizumab hindered B cell maturation. Tocilizumab could potentially therefore improve the long-term efficacy of desensitization, by limiting anti-HLA rebound and thus preventing antibody-mediated rejection. This hypothesis is supported by a recent study that used clazakizumab (a monoclonal antibody directed against IL-6) in combination with standard-of-care. In this study, clazakizumab was continued after kidney transplantation. The results were encouraging: 9/10 patients received a transplant, and 6 months post-transplant none of them had developed donor-specific antibodies.ConclusionIL-6 pathway blockade monotherapy fails to desensitize highly sensitized kidney transplant candidates. In combination with standard-of-care, it does not appear to significatively improve kidney allograft access (short-term efficacy) vs. standard-of-care only. However, it could improve the long-term prognosis of HLA-incompatible transplant by orienting the response toward a tolerogenic profile, by hindering B-cell maturation and thereby preventing DSA rebound after transplantation. This hypothesis requires confirmation in further studies. | ||
| 786 | 0 | _nNéphrologie & Thérapeutique | Volume 18 | 7 | 2022-07-26 | p. 577-583 | 1769-7255 | |
| 856 | 4 | 1 | _uhttps://shs.cairn.info/journal-nephrologie-therapeutique-2022-7-page-577?lang=en |
| 999 |
_c192092 _d192092 |
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